CD45RA Depleted Peripheral Stem Cell Addback to Prevent Graft versus Host Disease and Infection after Alternative Donor TCRalpha beta/CD19 Depleted Hematopoietic Stem Cell Transplant

Status: active

This phase I/II trial tests the safety, side effects and best dose of CD45RA depleted T cells and how well it works in preventing graft-versus-host disease (GVHD) and viral and fungal infections in patients after receiving T cell receptor (TCR) alpha beta/CD19 depleted hematopoietic stem cell transplant from an alternative donor. Sometimes the transplanted cells from a donor can attack the body's normal cells (called GVHD) and transplants involving an alternative donor, such as an unrelated donor or a mismatched family donor, have a higher risk of GVHD and developing life-threatening infections. It has been proven that TCR alpha beta/CD19 depleted T cells (a type of white blood cell) from an alternative donor is effective in preventing GVHD but the immune system may be slow to recover which can increase the risk of infection. This trial uses a new method of processing donated stem cells, the CliniMAC device, to remove (deplete) the TCR alpha beta/CD19 positive T cells as well as CD45RA positive T cells from a portion of the donated cells. CD45RA positive T cells are known to be associated with GVHD. Giving CD45RA depleted T cells may speed up immune system recovery and decrease the risk of GVHD and life-threatening infections in patients after a TCR alpha beta/CD19 depleted T cell stem cell transplant from an alternative donor.

Inclusion Criteria

PATIENT: Patients ≤ 25 years
PATIENT: Disease eligibility * Diagnosis for which allogeneic hematopoietic stem cell transplant (HSCT) may be curative * These diagnoses include but are not limited to hematologic malignancies, primary immune deficiencies/dysregulation syndromes, bone marrow failure syndromes, and hemoglobinopathies * Remission status of hematologic malignancies and additional disease-specific eligibility determinations will be according to standards of practice within the Children's Hospital of Philadelphia (CHOP) Cellular Immunotherapy and Transplant Program. Disease eligibility for study participation will be determined solely on whether a patient has been determined to be eligible for transplant on a clinical basis
PATIENT: Organ function and infectious status as per our CTTS standards of care
PATIENT: Signed consent by parent/legally authorized representative or able to give consent if ≥ 18 years
PATIENT: Participants of childbearing potential must have a negative pregnancy test as per institutional standards of practice (SOP)
DONOR: Unrelated donor meets national marrow donor program criteria for donation
DONOR: Related donor (at least haploidentical) willing and able to donate mobilized peripheral stem cells
DONOR: Infectious disease testing per standard of care
DONOR: HLA testing/matching * HLA testing to be done by molecular methods for A, B, C, DRB1, DQB1 * Related donor: Must be ≥ 5/10 match * Unrelated donor: 10/10 or 9/10 match * Killer-cell immunoglobulin-like receptors (KIR) typing for haploidentical donor for hematologic malignancies * Donor specific HLA antibodies (DSA) should be assessed for all subjects receiving an HLA mismatched graft (≤ 9/10)
DONOR: Donor must be willing to undergo granulocyte colony-stimulating factor (GCSF) mobilization and peripheral blood stem cell collection
DONOR: Donors must be willing to sign consent to participate in this study. Stem cells will be manipulated under an investigational device exemption (IDE). Unrelated donors will sign a consent with the National Marrow Donor Program (NMDP), and related donors will sign a consent for CHOP’s institutional review board (IRB) approved collection study, under IRB# 04-004078

Exclusion Criteria

PATIENT: Patients who have performance score < 60
PATIENT: No suitable donor available for mobilized peripheral stem cells
PATIENT: Patients with Hodgkin lymphoma or non-Burkitt, non-lymphoblastic lymphoma
PATIENT: Planned receipt of alemtuzumab during conditioning
PATIENT: Patients with an available and suitable 10/10 HLA matched sibling donor

PRIMARY OBJECTIVES:

I. Safety evaluation assessment by cumulative incidence of acute and chronic GVHD following CD45RA-depleted donor T-lymphocytes (CD45RA depleted addback) in patients receiving TCR alpha/beta/CD19-depleted allogeneic hematopoietic progenitor cells (TCR alpha beta/CD19) depleted peripheral blood stem cells from unrelated donors or ≥ 5/10 human leukocyte antigen (HLA) matched related donors.

II. Evaluate tempo of immune reconstitution following TCRalpha beta/CD19 depleted HSCT with CD45RA+ depleted addback, compared to historical experience with TCRalpha beta/CD19 depletion alone.

III. Evaluate incidence of viral (cytomegalovirus [CMV], adenovirus, Epstein-Barr virus [EBV], BK) reactivation following TCRalpha beta/CD19 depleted HSCT with CD45RA depleted addback, compared to historical experience with TCRalpha beta/CD19 depletion alone.

OUTLINE: This is a phase I, dose-escalation study of CD45RA depleted T-cell addback followed by a phase II study.

DONOR: Related donors undergo leukapheresis on day -1 or on day 0. Unrelated donors undergo leukapheresis on day -2 and/or day -1.

PATIENT: Patients receiving conditioning therapy per standard of care. Patients receive TCRalpha beta/CD19 depleted T cells intravenously (IV) on day 0 and CD45RA depleted T cell infusion on day 10.

After completion of study treatment, patients are followed at least weekly up to day 100 then at least monthly until day 365.

Have a question?
We're here to help

Chat with us: LiveHelp
Call us: 1-800-4-CANCER
(1-800-422-6237)

Which trials are right for you?

Use the checklist in our guide to gather the information you’ll need.

CD45RA Depleted Peripheral Stem Cell Addback to Prevent Graft versus Host Disease and Infection after Alternative Donor TCRalpha beta/CD19 Depleted Hematopoietic Stem Cell Transplant

Inclusion Criteria

Exclusion Criteria

United States

Pennsylvania

Philadelphia

Have a question?
We're here to help

Which trials are right for you?

CD45RA Depleted Peripheral Stem Cell Addback to Prevent Graft versus Host Disease and Infection after Alternative Donor TCRalpha beta/CD19 Depleted Hematopoietic Stem Cell Transplant

Description

Eligibility Criteria

Locations & Contacts

Trial Objectives and Outline

Trial Phase & Type

Lead Organization

Trial IDs

Have a question?We're here to help

Which trials are right for you?

Have a question?
We're here to help